Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia.
Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

Department of Medicine

This recent paper in Circulation, from Arshed Quyyumi and colleagues at the Emory Clinical Cardiovascular Research Institute, can be seen as a culmination of, even vindication for, Â Dean Jones’ ideasÂ about redox biology.

We now know that free radicals, in the form of reactive oxygen species, can sometimes be good, even essential for life. So antioxidants that soak up free radicals to relieve you of oxidative stress: that doesn’t seem to work.

Dean Jones, who is director of Emory’s Clinical Biomarkers laboratory,Â has been an advocate for a different way of looking at oxidative stress. That is, instead of seeing cells asÂ big bags of redox-sensitive chemicals, look at cellular compartments. Look at particular antioxidant proteins and sulfur-containing antioxidant molecules such asÂ glutathione and cysteine.

That’s what theÂ Circulation paper does. Mining the Emory Cardiovascular Biobank, Quyyumi’s team shows that patients with coronary artery disease have a risk of mortality that is connected to the ratio of glutathione to cystine (the oxidized form of the amino acid cysteine).

One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics withÂ non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.

As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrhealÂ Immodium, can make bacteria sensitive toÂ tetracycline-type antibiotics.

Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.

“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.

Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. SheÂ and her colleagues have been investigatingÂ compounds that can disruptÂ biofilms, thusÂ enhancingÂ antibiotic activity. More at eScienceCommonsÂ and at her lab’s site.

To prevent auto-immune attack, our bodies avoid making antibodies against molecules found on our own cells. That leaves gaps in our immune defenses bacteria could exploit. Some of those gaps are filled by galectins, a family of proteins whose anti-bacterial properties were identified by Emory scientists.

In the accompanying video, Sean Stowell, MD, PhD and colleagues explain how galectins can be compared to sheep dogs, which are vigilant in protecting our cells (sheep) against bacteria that may try to disguise themselves (wolves).

The video was produced to showcase the breadth of research being conducted within Emoryâ€™s Antibiotic Resistance Center. Because of their ability to selectively target some kinds of bacteria, galectins could potentially be used as antibiotics to treat infections without wiping out all the bacteria in the body. Read more

Emory rheumatologist Arezou Khosroshahi was the lead author on a differential diagnosisÂ case report in New England Journal of MedicineÂ published in October, which describesÂ an example of IgG4-related disease. This autoimmune conditionâ€™s name was agreed upon only recently, at an international conference she co-directed in 2011.

This review calls IgG4-related disease an â€œorphan disease with many faces.â€Â It sounds like each case has the potential to be an episode of House. As Khosroshahi explains:

â€œMost patients undergo invasive procedures for resection or biopsy of the affected organ to exclude other conditions. Unfortunately, most of those patients get dismissed by the clinicians, given the good news that their disease was not malignancy. Many of them have recurrence of the condition in other organs after a few months or years.â€

Rheumatologist Arezou Khosroshahi, MD

In the case report, a woman was admitted to Massachusetts General Hospital, because of shoulder and abdominal pain and an accumulation of fluid around her lungs. Surgeons removed a softball-sized mass from her right lung. The mass did not appear to be cancerous, but instead seemed to be the result of some kind of fibrous inflammation, and the patientÂ was treated with antibiotics. Read more

A common cause of bone loss is an overactive parathyroid gland, which doctors usually treat with surgery. New research on how excess parathyroid hormone affects immune cells suggests that doctors could repurpose existing drugs to treat hyperparathyroidism without surgery.

The results were publishedÂ October 8 inÂ Cell Metabolism. [My apologies for not posting thisÂ in October.]

“Surgery is sometimes not an appropriate remedy for hyperparathyroidism because of the condition of the patient, and it is also expensive,” says lead author Roberto Pacifici, MD. “Also, the one pharmacological treatment that is available, cinacalcet, is not always the ideal solution. This work could potentially lead to alternatives.”

Roberto Pacifici, MD

Researchers at Emory University School of Medicine led by Pacifici teamed up with doctors from the University of Turin in Italy, combining observations of human patients with an overactive parathyroid with experiments on mice.

The drugs identified as potential treatments are: calcium channel blockers, now used to treat high blood pressure, and antibodies that block the inflammatory molecule IL-17A, under development for the skin disease psoriasis. Clinical trials would be necessary to show that these drugs are effective against parathyroid hormone-induced bone loss in humans. Read more

Stem cell biologist Young-sup Yoon and colleagues recently published a paper in Biomaterials in which the authors use chitosan, a gel-like carbohydrate material obtainedÂ by processing crustacean shells, to aid in cell retention and survival. Ravi Bellamkonda’s lab at Georgia Tech contributed to theÂ paper.

More refinement of these approaches are necessary before clinical use, Â but it illustrates how engineered mixtures of progenitor cells and supportive materials are becoming increasingly sophisticated and complicated.

The chitosan gelÂ resemblesÂ the alginate material used to encapsulate cellsÂ by the Taylor lab.Â Yoon’s teamÂ wasÂ testing efficacy in a hindlimb ischemia model, in which a mouseâ€™s leg is deprived of blood. This situation is analogous to peripheral artery disease, and the readout of success is the ability of experimental treatments to regrow capillaries in the damaged leg.

The current paper builds a bridge between the nurse and building block approaches, because the researchers mix two complementary types of cells: an angiogenic one derived from bone marrow cells that expands existing blood vessels, and a vasculogenic one derived from embryonic stem cells that drives formation of new blood vessels.Â Note: embryonic stem cells were of mouse origin, not human. Read more

I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.

However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.

To that list, we could add the accumulation of microparticles, tiny membrane-clothed bags that contain proteins and RNA, which have effects on blood vessels and the immune system upon transfusion. Note: microparticles are similar to exosomes but larger â€“ the dividing line for size is about 100 nanometers. Both are much smaller than red blood cells.

EUH blood bank director John Roback recently gave a talk on the blood storage issue, and afterwards, cardiologist Charles Searles and research fellow Adam Mitchell were discussing their work on microparticles that come from red blood cells (RBCs). They have been examining the effects RBC-derived microparticles have on endothelial cells, which line blood vessels, and on immune cellsâ€™ stickiness.

Mitchell mentioned that he had some striking electron microscope images of microparticles and some of the particles looked like worms. With the aim of maintaining Lab Landâ€™s â€œCool Imageâ€ feature, I resolved to obtain a few of his photos, and Mitchell generously provided several.

â€œThose worms definitely had me mesmerized for a while,â€ he says.

In his talk, Roback described some of the metabolomics research he has been pursuing with Dean Jones. Instead of focusing only on how long blood should be stored, Robackâ€™s team is examining how much differences between donors may affect donated bloodâ€™s capacity to retain its freshness. Read more

People with systemic lupus erythematosus can experience a variety of symptoms, such as fatigue, joint pain, skin rashes and kidney problems. Often the symptoms come and go in episodes called flares. In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.

A team of Emory scientists has been investigating some fundamental questions about lupus: where do the cells that produce the self-reactive antibodies come from? Are they all the same?

In the accompanying video, Kelli Williams, who helps study the disease and has lupus herself, describes what a flare feels like. In addition, Emory researchers IÃ±aki Sanz, MD and Chris Tipton, PhD explain their findings, which were published this summer inÂ Nature Immunology.

Judging by the number and breadth ofÂ abstractsÂ on lupus at the Department of Medicine Research DayÂ (where Tipton won 1st place for basic science poster),Â more intriguing findings are in the pipeline. Goofy Star Wars metaphors and more explanations of the scienceÂ here.

A recent study concluded that itâ€™s more difficult for adults today to maintain the same weight as those a few decades ago, even with the same levels of food intake and exercise.Â On one level, this news is comforting to anyone in middle age, who may have been athletic as a teenager in the 1980s but isnâ€™t anymore. Itâ€™s just harder nowadays!

However, the study authors also suggested, in an interview with The Atlanticâ€™s Olga Khazan, an array of factors that might be contributing to the rise in obesity: exposure to chemicals such as pesticides and flame retardants, prescription drugs such as antidepressants, and altered microbiomes linked with antibiotic use in livestock.

The heavy metal cadmium may belong on that list of chemicals, not primarily as a booster of obesity, but insteadÂ in connection with the increase in prevalence in NAFLD (non-alcoholic fatty liver disease) over the last few decades.

Researchers led by Young-Mi Go and Dean Jones exposed mice to low levels of cadmium, so that the amounts of cadmium in their livers were comparable to those present in average middle age Americans, without tobacco or occupational exposure.Â They observed that cadmium-treated mice had more fat accumulation in the liver and elevated liver enzymes in their blood, compared with control mice with 10 times less cadmium.

Cadmium accumulates in the body over time. Tobacco smoke and the industrial workplace can be routes for cadmium exposure, but food is the major source for most non-smokers. Until the 1990s, most batteries were made with cadmium, and much cadmium production still goes into batteries. It is also found in paint and in corrosion-resistant steel. Read more